Scientists Find New Tricks For Old Drugs
Most drugs have side effects, but sometimes they're actually good news.
Researchers are now exploring whether some cheap and common drugs have side effects that could help people fight off the flu and other lung infections.
This idea has a passionate advocate: Dr. David Fedson. About 10 years ago, this infectious disease specialist had a disturbing thought. He was working in the vaccine industry in France, and he started to wonder what would happen if, all of a sudden, the world was gripped with a flu pandemic.
One hundred years ago, the 1918 Spanish flu pandemic swept the globe, killing 50 million people, or maybe more. Scientists fear a similar pandemic is only a matter of time. What then? Fedson wondered.
"No company had a strategy for dealing with the pandemic," he says. "And also when you just looked at the arithmetic about how quickly they'd need literally billions of doses of the vaccine, which they couldn't make in time, it became very clear the you simply can't get there from here."
Antiviral medications like Tamiflu are expensive and far from perfect. So Fedson decided what the world needed was a cheap and simple drug that wouldn't cure the flu, but would help people weather the symptoms and survive.
He focused on drugs that would tamp down inflammation, which can make an infection deadly, "so that's the general idea that I've been working on over the course of this last decade."
That led him to think about the world's most widely prescribed drugs, the statins – and it also led him to Dr. Jeffrey Jacobson, a lung specialist who studies the unusual properties of statins at the University of Illinois at Chicago.
"It's been long recognized that these drugs do a whole lot more than just lower cholesterol levels," Jacobson says.
They also reduce inflammation by interrupting some of these potentially deadly processes. Of particular concern, inflammation generates a "storm" of molecules that can overstimulate the immune system. Blood vessels can also become dangerously leaky.
Jacobson has been studying the drugs to see if they can help people with severe lung infections. They don't attack the virus directly, but "if we can do something to protect people during the course of their infection or injury we ideally would buy them enough time to survive," Jacobson says.
"These drugs are readily available, they're pretty darned cheap all things considered, and they're relatively safe," he says. "So it's sort of a win-win-win if we can actually demonstrate that these have protective and beneficial effects."
Studies to date have been mixed, but some suggest there's a benefit. One study found that people who were already taking statins when the flu stuck did better than patients who weren't on these drugs.
That doesn't necessarily mean the drug is beneficial – it could simply be a sign that someone is getting good medical care. "It might mean that you see your doctor more regularly and they put you on a statin as a preventive measure for high cholesterol," says Dr. Maureen Chase, an emergency physician at the Harvard-affiliated Beth Israel Deaconess Medical Center in Boston.
Five years ago, Chase and her colleagues at the hospital decided to put statins to the test. They have been randomly giving a placebo or atorvastatin, the generic name for Lipitor, to patients who show up in the emergency room with the flu.
They're asking a simple question: "If you are currently not taking a statin medication, and we give you a statin medication, do you have better outcomes than those not taking a statin medication?"
Chase has finally studied enough people to answer that question. She's now analyzing her results, and hopes to have the work done by the next flu season.
"This would be a great additional therapy to what we already have to treat influenza, and could be used in a worldwide fashion" she says. "So if effective, this could have fantastic public health implications."
Other scientists wonder whether other existing drugs might also do the trick. Michel Cousineau is president of a French company called Signia Therapeutics. It grows human lung cells in the lab and uses them to identify old or failed drugs that might unexpectedly work against respiratory diseases. He says the company has singled out two old high-blood-pressure drugs, etilefrine and diltiazem (brand name Cardizem, among others), and they're now being tested in French hospitals against the flu.
"In France there's something called the reanimation center, and that's where people end up when they are at high risk of dying," Cousineau says. The French government is sponsoring a clinical trial involving 300 patients at these centers to test these drugs. "Currently they have very limited options other than hoping that nature will do its work," Cousineau says.
This is also a potential business opportunity. Cousineau says his company is trying to "reposition" these old drugs into a new market. Unlike statins, available for a few dollars a month, they won't necessarily be cheap. Part of the company's business plan is to make these drugs available in inhaled form – and that advance would give the company new opportunities for patents and licensing deals.
His company is also interested in exploring drugs that never quite made it to the market. Many potential drugs pass a battery of expensive safety tests, but they fail to work for the disease they're being developed to combat. "There was a huge cost to bring them up to that point, and they're generating no revenue," he says. Maybe some can be "recycled" into new drugs.
This is not an outlandish idea. Cousineau said that in recent years, scientists have come to realize that the typical drug actually has six to 12 biological "targets" in the body. When drugs hit some of those targets, there can be nasty side effects. But in other cases the interaction has the potential to be therapeutic.
Fedson, the retired vaccine researcher, tried an audacious idea in this vein during the 2014 Ebola outbreak in West Africa. He got excited about the possibility that some of the nontraditional approaches for treating the flu could also work to help shore up Ebola patients' fragile lungs and blood vessels.
"If something appears to work, or seems to be a good candidate ... against influenza, it ought to work against other diseases which share some of the same biochemical pathways," he reasons. "And Ebola is one of them."
He couldn't get pharmaceutical companies interested in this. They were focused on potential new drugs and vaccines that attacked the virus directly. "The idea that you can take something that's old, generic, inexpensive and that shores up the host response is of no interest to them at all," Fedson says.
But he generated some publicity around this idea, including an op-ed in The New York Times and ultimately caught the attention of a Norwegian doctor who had an interest in African health matters.
"Bless his heart, he took his own money and eventually spent $25,000 of his own money to buy a supply of three drugs," Fedson says. That included statins as well as two other medicines, an angiotensin-receptor blocker and clomiphene.
"He sent these drugs to Sierra Leone with the understanding that the drugs would be administered according to whatever decisions were made by health authorities and physicians in Sierra Leone," Fedson says.
The African physicians sent out mixed signals about the results of their experiences, and they never published their findings. So it's not clear what, if anything, they learned about these drugs.
You can contact Richard Harris at[email protected].
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